Version July 2025
ASCVD: atherosclerotic cardiovascular disease; FH: familial hypercholesterolemia; LDL-C: low-density lipoprotein cholesterol; PCSK9: proprotein convertase subtilisin kexin type 9.
* Homozygous FH is usually diagnosed in childhood. Refer to separate UpToDate content regarding treatment of FH in children and adolescents.
¶ Rosuvastatin 40 mg orally once daily and atorvastatin 80 mg orally daily are appropriate doses for most adults. If the patient is pregnant, breastfeeding, or trying to conceive, statins and most other lipid-lowering medications are contraindicated.
Δ Some experts try a different high-potency statin, while others add a second-line medication (eg, ezetimibe, PCSK9 inhibitor).
◊ Myalgias are a common reason for statin nonadherence. Consider restarting the statin at a lower dose, trying a different statin, or proceeding to a second-line medication (eg, ezetimibe, PCSK9 inhibitor).
§ Very high risk refers to the presence of clinically evident ASCVD. High risk refers to the presence of subclinical ASCVD or diabetes mellitus. Low risk refers to the absence of ASCVD and diabetes mellitus. For patients at low risk, most experts recommend a goal LDL-C of ≤100 mg/dL (2.6 mmol/L), but some recommend a goal of ≤70 mg/dL (1.8 mmol/L) for certain patients. Refer to UpToDate content on treatment of FH for discussion.
¥ Patients whose LDL-C is above their goal by at least 25% are unlikely to reach their goal on ezetimibe alone.
‡ The choice among PCSK9 inhibitors (eg, alirocumab, evolocumab, inclisiran) is based on availability, cost, and patient preference. Additionally, some insurers may require a trial of ezetimibe before a PCSK9 inhibitor may be prescribed. For patients on a PCSK9 inhibitor, LDL-C should be measured at the nadir of drug effect (ie, shortly before the next dose is due). Refer to UpToDate content on PCSK9 inhibitors and individual drug monographs for more details.
† Evaluate for causes of secondary hypercholesterolemia and treat if necessary. If none are present, refer to a lipid specialist. Refer to UpToDate content on treatment of refractory hypercholesterolemia in patients with FH.
